Mycobacterium genavense infections in immunocompromised patients with HIV: A clinical case report

Key Clinical Message It is essential to consider non‐tuberculosis mycobacterium in HIV‐positive patients with fever, abdominal pain, weight loss, and splenomegaly. Abstract Mycobacterium genavense is an opportunistic slow‐growing nontuberculous mycobacterium in patients with immunocompromised backgrounds, especially HIV‐positive patients. In this study, we present two cases of Mycobacterium genovese infection in HIV‐positive patients with a good clinical response to accurate treatment.


| INTRODUCTION
Mycobacterium genavense is an opportunistic slowgrowing mycobacterium in patients with immunocompromised backgrounds, especially HIV-positive patients.It was first discovered in an HIV-positive patient in Geneva, Switzerland. 1,2t can manifest as fever, night sweats, and weight loss along with other symptoms such as abdominal pain, nausea, vomiting, and diarrhea when the gastrointestinal tract is involved.The symptoms are similar to those with Mycobacterium avium complex (MAC) disseminated infections. 3,4Smear examination from sterile sites such as blood, bone marrow, lymph nodes, and spleen and also blood culture are necessary for the diagnosis. 5,6Early diagnosis and proper treatment with rifampin plus another antituberculosis drug such as clarithromycin or doxycycline is essential. 7Despite combinational therapy, the overall mortality is high, especially in HIV-positive patients however, patients who receive macrolide-containing regimens are believed to have a better prognosis. 8ue to the rare presentation of M. genovese, the diagnostic and therapeutic challenges we present two cases of HIV-positive patients with M. genovese infection and their clinical process.This study is the first report of HIVpositive M. genovese infection in Iran.

| Case history/examination
A 26-year-old male without any history of previous medical problems was admitted to the Imam Khomeini Medical Complex, Tehran, Iran with fever, abdominal pain, nausea, vomiting, and non-bloody diarrhea for a month after several outpatient therapies.He has had a severe weight loss of about 30 kg in the last 5 years without any dietary problems.His abdominal pain was periumbilical concomitant with nausea, vomiting, and anorexia.The abdominal pain radiated to the back and escalated with food consumption.
In his social history, the patient reported one time of unprotected sexual intercourse about 7 years ago and an opioid addiction for 10 years.
On physical examination, he was severely pale, had a temperature of 38°C, and diffuse oral candidiasis.Epigastric and periumbilical tenderness along with mild splenomegaly was detected during abdominal examination.

| Methods
Primary laboratory test results are in favor of positive HIV along with pancytopenia (Tables 1 and 2).Positive HIV was confirmed with enzyme-linked immunosorbent assay (ELISA).
Sputum smear, culture, and polymerase chain reaction (PCR) were negative for Mycobacterium tuberculosis.According to severe abdominal pain, surgical consultation was done.After acute surgical and medical abdomen were ruled out, abdominopelvic sonography and CT scan were performed (Figures 1 and 2).Cryptosporidium was positive in stool examination and esophageal candidiasis along with erythematous mucosal tissue were detected during endoscopic and colonoscopic examinations.
According to the positive HIV tests, non-bloody diarrhea, splenomegaly, pancytopenia, mesenteric lymphadenopathies, Mycobacterium tuberculosis, atypical mycobacterial infections, and lymphoma were suspected.Bone marrow aspiration and biopsy showed hypocellularity which could be explained according to the positive HIV condition.The Mycobacterium and non-mycobacterial tuberculosis bone marrow PCRs were all negative.

| Conclusion and results
Considering the negative results of bone marrow culture and PCR, a CT scan-guided biopsy of mesenteric lymph nodes was obtained.According to the positive PCR for M. genovese, rifabutin 300 mg/daily, ethambutol 800 mg/ daily, azithromycin 500 mg/daily, levofloxacin 500 mg/ daily, and amikacin 500 mg/q12h were prescribed.Additional treatments include fluconazole 400 mg /daily for oral candidiasis, TRUVADA (combination of emtricitabine and tenofovir disoproxil fumarate) once daily, and dolutegravir once daily as antiviral agents, and cotrimoxazole as a prophylactic agent were started (these treatments cover both positive HIV and cryptosporidium).
About 10 days after starting the effective treatment, the fever and abdominal pain disappeared, and the patient was discharged with azithromycin 500 mg, ethambutol 800 mg, levofloxacin 750 mg, and rifabutin 300 mg once a day, and the continuation of the antiviral drugs, as well as cotrimoxazole for about 1 year.

| Case history/examination
A 35-year-old intravenous drug user male without any history of previous medical problems was admitted to the Imam Khomeini Medical Complex, Tehran, Iran with fever, weight loss, weakness, dysphasia, and odynophagia for 2 months.He has had periodic exertional dyspnea, night fever, and epigastric non-positional abdominal pain without any radiation.In his social history, he reported methadone and methamphetamine addiction.On physical examination, he was severely pale, cachexic, had a temperature of 39°C, and diffuse oral and pharyngeal candidiasis.Mild hepatosplenomegaly was detected during abdominal examination which was confirmed by abdominal sonography.

| Methods
Considering the patient's high-risk behaviors and oral candidiasis, a rapid HIV test was done.The positive rapid HIV test was confirmed using ELISA.The patient's primary laboratory test results are summarized in Tables 3  and 4. Intravenous fluconazole was started and the candidiasis, dysphagia, and odynophagia were dissolved after 72 h.Endoscopic and colonoscopic examinations were in favor of candidiasis esophagitis.Further evaluations with an abdominopelvic CT scan were done (Figures 3 and 4).
According to fever, bicytopenia, hepatosplenomegaly, and positive HIV results, Mycobacterium, nonmycobacterium tuberculosis, and also lymphoma were suspected.Along with liver and bone marrow biopsy, the 4-drug "HREZ" fixed-dose combination with isoniazid (H)-rifampicin (R)-ethambutol (E)-pyrazinamide (Z) plus levofloxacin, TRUVADA and dolutegravir as antiviral agents were started.Based on liver biopsy M. genavense type 1 was detected.Despite the expectation, bone marrow PCR was negative for M. genavense.

| Conclusion and results
Based on the liver biopsy results, anti-TB drugs were discontinued and the patient was given azithromycin 500 mg, levofloxacin 750 mg, rifabutin 300 mg, and ethambutol 800 mg once a day.After 2 weeks of treatment, fever and abdominal pain were dissolved and the patient was discharged with azithromycin, rifabutin, lofloxacin, ethambutol, and the continuation of the antiviral drugs.Anti-TB treatment was started in this patient due to prolonged fever, and severe abdominal pain and due to the long process of preparing the biopsy and PCR results, and the treatments were changed when the results were prepared and the diagnosis was determined.F I G U R E 1 Chest CT scan.An 8-mm subpleural nodule was observed in the lateral segment of the lower lobe of the right lung (RLL).

| Discussion
Mycobacterium genavense is an opportunistic slowgrowing non-tuberculous mycobacterium affecting patients with underlying immunosuppressive disorders, especially HIV-positive patients with CD4 counts <100.Its pathogenicity is similar to MAC. 9,10 Other immunocompromised patients such as solid organ and hematopoietic stem cell recipients, patients with sarcoidosis, and patients with chronic steroid or other immunomodulator drug use are in danger of disseminated M. genavense infection. 11,12n this case report, we present two male HIV-positive patients who were diagnosed with M. genavense infection.
Based on the meta-analysis by Wetzstein et al. 76.7% of the patients with M. genavense infection were HIVpositive, and 79.8% were male. 8Men are believed to have a higher probability of M. genavense infection due to a higher proportion of males among individuals with HIV infection. 10he combination therapy with azithromycin, levofloxacin, amikacin, rifabutin, and ethambutol is essential to overcome M. genavense infection in patients with or without HIV.Good clinical and radiological treatment responses were seen after the proper treatment.In our patients, after 2 weeks of therapy, the patients were discharged with improved symptoms and acceptable clinical conditions. 13I G U R E 2 Abdomio-pelvic CT scan.Mild splenomegaly (150 mm) and multiple mesenteric lymphadenopathies, with a conglomeration pattern and maximum size of 17 mm were detected.recent studies in our country, HIV-positive patients with fever, abdominal pain, splenomegaly, and weight loss were considered to have TB infection.Due to the similarity of the treatment choices and the M. genavense relative response to TB therapy, the diagnosis was not distinguished.However; it is important to consider non-tuberculosis mycobacterium such as M. genavense in HIV-positive patients with mentioned symptoms and positive Ziehl-Neelsen stain and start specific treatments. 14Based on our knowledge this study was the first case report on M. genavense in HIV-positive patients in Iran.F I G U R E 3 Chest CT scan.There was no abnormal finding.
In conclusion, was the first report demonstrating M. genavense infection among HIV-positive patients in Iran.It is essential to consider non-tuberculosis mycobacterium in HIV-positive patients with fever, abdominal pain, weight loss, and splenomegaly.Timely diagnosis and proper treatment will reduce mortality and morbidity rates.
Laboratory test results.
Laboratory test results.
Note:a Normal ranges are provided within the parenthesis.T A B L E 4